Apolipoprotein E: A pathological chaperone protein in patients with cerebral and systemic amyloid

Many biochemically diverse proteins can give rise to amyloid fibrils; however, they are all accompanied by P component and glucosaminoglycans. With antibodies specific to apolipoprotein E (apo E) we used immunohistochemical techniques to test for the presence of this protein in both cerebral and systemic amyloid. We found apo E immunoreactivity in all tested types of cerebral and systemic amyloid. In amyloid deposits apo E P, component and glucosaminoglycans may be acting as 'pathological molecular chaperones'. The latter we define as a group of unrelated proteins that induce beta-pleated conformation in amyloidogenic polypeptides.

[1]  R. Mahley,et al.  Interaction of plasma lipoproteins containing apolipoproteins B and E with heparin and cell surface receptors. , 1979, Biochimica et biophysica acta.

[2]  P. Lipsky,et al.  Modulation of human lymphocyte responses by low density lipoproteins (LDL): enhancement but not immunosuppression is mediated by LDL receptors. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. V. van Duinen,et al.  Isolation and characterization of amyloid P component from Alzheimer's disease and other types of cerebral amyloidosis. , 1988, Laboratory investigation; a journal of technical methods and pathology.

[4]  K. McAdam,et al.  Human Amyloid P Component: An Elastase Inhibitor , 1984, Scandinavian journal of immunology.

[5]  R. Kisilevsky,et al.  Sulfated glycosaminoglycans: a common constituent of all amyloids? , 1987, Laboratory investigation; a journal of technical methods and pathology.

[6]  L. Sternberger,et al.  Leakage and neuronal uptake of serum protein in aged and Alzheimer brains. A postmortem phenomenon with antemortem etiology. , 1991, Laboratory investigation; a journal of technical methods and pathology.

[7]  J. Ellis.  Proteins as molecular chaperones , 1987, Nature.

[8]  C. Kay,et al.  Circular-dichroism studies on two murine serum amyloid A proteins. , 1988, The Biochemical journal.

[9]  M. Picken,et al.  Distribution of the Protease Inhibitor α1Antichymotrypsin in Cerebral and Systemic Amyloid , 1990 .

[10]  J. Rothman.  Polypeptide chain binding proteins: Catalysts of protein folding and related processes in cells , 1989, Cell.

[11]  J. Taylor,et al.  Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. , 1985, The Journal of clinical investigation.

[12]  M. Pras,et al.  Characterization of High Molecular Weight Amyloid A Proteins , 1991, Scandinavian journal of immunology.

[13]  E. Shooter,et al.  A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. , 1989, The Journal of clinical investigation.

[14]  F. Tagliavini,et al.  Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals , 1988, Neuroscience Letters.

[15]  B. Trapp,et al.  Oligodendrocytes but not astrocytes express apolipoprotein E after injury of rat optic nerve , 1989, Glia.

[16]  R. Mahley,et al.  Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. , 1988, Science.

[17]  B. Frangione,et al.  Systemic and cerebral amyloidosis. , 1989, Annals of medicine.

[18]  M. Pras,et al.  The amino acid sequence of a major nonimmunoglobulin component of some amyloid fibrils. , 1972, The Journal of clinical investigation.

[19]  G. Plant,et al.  Familial cerebral amyloid angiopathy with nonneuritic amyloid plaque formation. , 1990, Brain : a journal of neurology.

[20]  S. Aota,et al.  Molecular cloning and nucleotide sequence of cDNA for murine senile amyloid protein: nucleotide substitutions found in apolipoprotein A-II cDNA of senescence accelerated mouse (SAM). , 1986, Nucleic acids research.

[21]  E. Otomo,et al.  Apolipoprotein E immunoreactivity in cerebral amyloid deposits and neurofibrillary tangles in Alzheimer's disease and kuru plaque amyloid in Creutzfeldt-Jakob disease , 1991, Brain Research.

[22]  V. Armstrong,et al.  Clinical relevance of the quantification of apolipoprotein E in cerebrospinal fluid. , 1991, Clinica chimica acta; international journal of clinical chemistry.

[23]  R. Mahley,et al.  Astrocytes synthesize apolipoprotein E and metabolize apolipoprotein E-containing lipoproteins. , 1987, Biochimica et biophysica acta.

[24]  J. Liepnieks,et al.  Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. , 1988, Biochemical and biophysical research communications.